Abstract P2-20-05: Personalized tumor vaccine can suppress tumor growth and metastasis in the syngeneic mouse breast cancer model
Authors: Hyeong-Gon Moon, Hye Youn Son, Woo Hang Heo, Mingji Quan, SONGBIN LI, Haritonova Valentina, Hamin Jeong, Wonshik Han, Han-Byoel Lee, YUJEONG HER, Ju Hee Kim
Journal: Cancer Research (2023)

Abstract Objective Immunotherapy using the tumor-specific antigens (TSAs) is a promising strategy in breast cancer. Studies have suggested that the in vivo exposures to certain tumors can induce adaptive anti-tumor immunity in syngeneic tumor models. In this study, we show the efficacy of the tumor lysate vaccine and peptide-based vaccine against tumor neoantigen in suppressing tumor growth and metastasis in 4T1 syngeneic tumor models. Method We used BALB/c mice and its syngeneic tumor cell lines to evaluate the anti-tumor effect induced by the transient exposure to the tumor cells. For tumor vaccines, we synthesized the tumor lysate vaccine by the freeze-thaw method or synthetic peptide against the selected tumor neoantigens identified by exome sequencing. We systemic and local immune remodeling was investigated by using immunohistochemistry, flow cytometry, and single cell RNA sequencing. Results We observed a significant reduction of tumor growth and metastasis in 4T1 syngeneic tumors when the mice were previously exposed to the same cells (pre-exposure group). This anti-tumor effect induced by the exposures to the tumor was cell line-specific. The 4T1 tumor lysate vaccines administered prior to the tumor cell injection also showed significant inhibitory effect on tumor growth and metastasis. T lymphocytes, isolated from the tumor tissues of the 4T1 pre-exposure mice and lysate vaccine-treated mice, showed higher levels of TNF-ɑ and IFN-ɣ when compared to the control those from the control tumors. The lysate vaccine treatment resulted in a substantial remodeling of tumor microenvironment including reduction of myeloid-derived suppressor cells and M2 tumor-associated macrophages. On the other hand, the numbers of M1 tumor-associated macrophages and effector memory CD8+ T cells were increased by the lysate vaccine. While the peptide vaccine showed no inhibitory effect on the primary tumor growth, it also suppressed spontaneous lung metastasis. Finally, we administered lysate tumor vaccine after the tumor establishment to determine the therapeutic effect. The lysate vaccine significantly suppressed the tumor growth and lung metastasis of the syngeneic 4T1 tumors. Conclusion Tumor lysate vaccine can suppress the tumor growth and metastasis in the 4T1 syngeneic mouse models by inducing substantial remodeling of tumor immune microenvironment. Additionally, tumor lysate vaccine can elicit similar anti-tumor immune response when administered after the establishment of the primary tumor suggesting a potential therapeutic value. Citation Format: Hyeong-Gon Moon, Hye Youn Son, Woo Hang Heo, Mingji Quan, SONGBIN LI, Haritonova Valentina, Hamin Jeong, Wonshik Han, Han-Byoel Lee, YUJEONG HER, Ju Hee Kim. Personalized tumor vaccine can suppress tumor growth and metastasis in the syngeneic mouse breast cancer model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-20-05.